Glutamate dehydrogenase (GLUD1) expression in breast cancer

Dysregulated cellular metabolism is regarded as one of the hallmarks of cancer with some tumours utilising the glutamine metabolism pathway for their sustained proliferation and survival. Glutamate dehydrogenase (GLUD1) is a key enzyme in glutaminolysis converting glutamate to α-Ketoglutarate for entry into the TCA cycle. Breast cancer (BC) comprises a heterogeneous group of tumours in terms of molecular biology and clinical behaviour, and we have previously shown that altered glutamine metabolism varies substantially among the different molecular subtypes. We hypothesise that the prognostic value of GLUD1 expression will differ between the BC molecular subtypes and may act as a potential therapeutic target for BC tumours.Methods: GLUD1 was assessed at the DNA, mRNA (n=1,980) and protein (n=1,300) levels in large and well-characterised cohorts and correlated with clinicopathological parameters, molecular subtypes, patient outcome and treatments. Results: There was a correlation between GLUD1 mRNA and GLUD1 protein expression which were highly expressed in low grade Luminal/ER+ BC (

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes

Prevalence and correlates of subjective cognitive impairment in Chinese psychiatric patients during the fifth wave of COVID-19 in Hong Kong

IntroductionThe extent of cognitive impairment and its association with psychological distress among people with pre-existing mental illness during COVID-19 is understudied. This study aimed to investigate prevalence and correlates of subjective cognitive impairment (SCI) in Chinese psychiatric patients during fifth-wave of COVID-19 in Hong Kong (HK).MethodsFour-hundred-eight psychiatric outpatients aged 18–64 years were assessed with questionnaires between 28 March and 8 April 2022, encompassing illness profile, psychopathological symptoms, coping-styles, resilience, and COVID-19 related factors. Participants were categorized into moderate-to-severe and intact/mild cognitive impairment (CI+ vs. CI-) groups based on severity of self-reported cognitive complaints. Univariate and multivariate regression analyses were conducted to determine variables associated with CI+ status.ResultsOne-hundred-ninety-nine participants (48.8%) experienced CI+. A multivariate model on psychopathological symptoms found that depressive and post-traumatic-stress-disorder (PTSD)-like symptoms were related to CI+, while a multivariate model on coping, resilience and COVID-19 related factors revealed that avoidant coping, low resilience and more stressors were associated with CI+. Final combined model demonstrated the best model performance and showed that more severe depressive and PTSD-like symptoms, and adoption of avoidant coping were significantly associated with CI+.ConclusionAlmost half of the sample of psychiatric patients reported cognitive complaints during fifth-wave of COVID-19 in HK. Greater depressive and PTSD-like symptom severity, and maladaptive (avoidant) coping were found as correlates of SCI. COVID-19 related factors were not independently associated with SCI in psychiatric patients. Early detection with targeted psychological interventions may therefore reduce psychological distress, and hence self-perceived cognitive difficulties in this vulnerable population

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Sulfonylurea Is Associated With Higher Risks of Ventricular Arrhythmia or Sudden Cardiac Death Compared With Metformin: A Population‐Based Cohort Study

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes

Sulfonylurea Is Associated With Higher Risks of Ventricular Arrhythmia or Sudden Cardiac Death Compared With Metformin: A Population‐Based Cohort Study

BACKGROUND: Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. METHODS AND RESULTS: Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. CONCLUSIONS: Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes

Table_1_Relationships between psychopathological symptoms, pandemic-related stress, perceived social support, and COVID-19 infection history: a network analysis in Chinese college students.docx

IntroductionPrevious coronavirus, 2019 (COVID-19) research has applied network analysis to examine relationships between psychopathological symptoms but rarely extended to potential risk and protective factors or the influence of COVID-19 infection history. This study examined complex inter-relationships between psychopathological symptoms, COVID-19–related stressors, perceived social support, and COVID-19 infection history among Chinese university/college students during the peak of fifth pandemic wave using a network analysis approach.MethodsA Least Absolute Shrinkage and Selection Operator–regularized partial correlation network using Gaussian graphical model was constructed in 1,395 Chinese university/college students in Hong Kong who completed a survey between 15 March and 3 April, 2022. Depressive, anxiety, and acute/traumatic stress symptoms were measured by Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Impact of Event Scale-6, respectively. COVID-19–related stressors and perceived social support were measured. Network differences by COVID-19 infection history (COVID-network vs. no_COVID-network) and network communities were examined.ResultsOur results showed that the most influential nodes were depressed mood, uncontrollable worries, and uncontrollable thoughts about COVID-19. The main bridging symptoms were concentration problems and psychomotor problems. The COVID-network, comprising participants with a history of COVID-19 infection only, was significantly stronger than the no_COVID-network. Perceived social support and stress from conflicts with family/friends formed a unique community with negative cognition and suicidal idea in the COVID-network only.ConclusionOur findings indicate that specific interventions targeting interpersonal conflicts and concentration problems as well as facilitating stress buffering effects of social support may represent effective strategies to reduce psychological distress in university/college students during COVID-19 and should be considered for future pandemic preparedness.</p

Table_1_Prevalence and correlates of subjective cognitive impairment in Chinese psychiatric patients during the fifth wave of COVID-19 in Hong Kong.DOCX

IntroductionThe extent of cognitive impairment and its association with psychological distress among people with pre-existing mental illness during COVID-19 is understudied. This study aimed to investigate prevalence and correlates of subjective cognitive impairment (SCI) in Chinese psychiatric patients during fifth-wave of COVID-19 in Hong Kong (HK).MethodsFour-hundred-eight psychiatric outpatients aged 18–64 years were assessed with questionnaires between 28 March and 8 April 2022, encompassing illness profile, psychopathological symptoms, coping-styles, resilience, and COVID-19 related factors. Participants were categorized into moderate-to-severe and intact/mild cognitive impairment (CI+ vs. CI-) groups based on severity of self-reported cognitive complaints. Univariate and multivariate regression analyses were conducted to determine variables associated with CI+ status.ResultsOne-hundred-ninety-nine participants (48.8%) experienced CI+. A multivariate model on psychopathological symptoms found that depressive and post-traumatic-stress-disorder (PTSD)-like symptoms were related to CI+, while a multivariate model on coping, resilience and COVID-19 related factors revealed that avoidant coping, low resilience and more stressors were associated with CI+. Final combined model demonstrated the best model performance and showed that more severe depressive and PTSD-like symptoms, and adoption of avoidant coping were significantly associated with CI+.ConclusionAlmost half of the sample of psychiatric patients reported cognitive complaints during fifth-wave of COVID-19 in HK. Greater depressive and PTSD-like symptom severity, and maladaptive (avoidant) coping were found as correlates of SCI. COVID-19 related factors were not independently associated with SCI in psychiatric patients. Early detection with targeted psychological interventions may therefore reduce psychological distress, and hence self-perceived cognitive difficulties in this vulnerable population.</p